LXRs/ABCA1 activation contribute to the anti-inflammatory role of phytosterols on LPS-induced acute lung injury
Daxue He, Shengquan Wang, Gaofeng Fang, Qian Zhu, Jingjing Wu, Jianling Li, Dan Shi, Xuemei Lian
Abstract
Phytosterols (PS) showed anti-inflammatory activities in acute lung injury (ALI), but the mechanism needs to be further elucidated. In this study, male C57BL/6J mice were gavaged with PS (75 mg/kg or 150 mg/kg) for 7 consecutive days, mice ALI were induced by tracheal instillation of LPS (50 μL, 1 mg/mL). In vitro, RAW264.7 cells were incubated with LPS in the presence or absence of 50 μM β-sitosterol. Enzyme-linked immunosorbent assay was used to detect levels of inflammatory cytokines. Real-time quantitative PCR and western blot analysis were used to detect changes in nuclear factor-kB (NF-κB) and liver X receptors (LXRs) pathways. The results showed that PS administration activated LXRs/ABCA1 pathway and significantly ameliorated LPS-induced pulmonary inflammation of ALI. The role of phytosterols was verified in LPS-stimulated RAW264.7 cells and the protective effect was weakened by administration of LXR antagonist GSK2033. These findings suggested that PS ameliorates LPS-induced ALI partially by activating the LXRs/ABCA1 pathway.